Epstein-Barr virus (EBV) is associated with two human tumors, Burkitt's lymphoma and nasopharyngeal carcinoma. In addition, reactivation of EBV infection in immunodeficient patients leads to a fatal lymphoproliferative disease. In vitro infection of B lymphocytes with EBV leads to a T-cell independent polyclonal activation and transformation of a smaller fraction of the infected cells. Although the molecular events underlying the processes of infection, transformation and polyclonal activation are still unknown, the first step involves the interaction of the virus with a specific receptor in the cell membrane. Our long-term goal is to understand the effects of viral binding on subsequent cellular events. In pursuit of this, we have been developing methods for the isolation of the EBV binding component (EBVR) found on Raji human lymphoblastoid cells. We have extracted and partially purified the EBVR from Raji cells. We have prepared an antibody specific for the receptor and we have significantly improved the purity of EBV virion preparations. We now propose to complete the purification and characterization of the EBVR. We will use a variety of affinity methods and conventional protein chemistry for this. We will then use the purified receptor and virus to initiate studies of their interactions. The data obtained should help to elucidate the role of the EBVR in viral infection, transformation and triggering cells to immunoglobulin production.